11β-HSD1 is an enzyme catalyzing the conversion of cortisone (inactive glucocorticoid) into cortisol (glucocorticoid), and is expressed primarily in the liver, visceral fat, etc. 11β-HSD1 functions locally and appears to serve as a factor amplifying intracellular cortisol levels in each organ. 11β-HSD1 is responsible for gluconeogenesis in the liver and is also related to accumulation of visceral fat. When the activity of this enzyme is inhibited, it is expected to provide a hypoglycemic effect in the liver due to inhibited gluconeogenesis and an inhibitory effect against fat accumulation in visceral fat. Thus, 11β-HSD1 inhibitors can be expected to be effective against obesity, impaired glucose tolerance, insulin resistance, hyperglycemia, hyperlipidemia, hypertension and metabolic syndrome (see Patent Document 1).
In addition, inhibition of 11β-HSD1 can suppress an increase in local glucocorticoid levels, and diseases whose conditions are ameliorated thereby include mental diseases (e.g., neurodegenerative disease, cognitive impairment, dementia, depression), osteoporosis, insufficient intraocular pressure-induced conditions including glaucoma (see Patent Document 1), vascular diseases and diabetic complications such as arteriosclerosis, cardiovascular disease, cerebral infarction, peripheral vascular disease, hypertension, diabetic nephropathy, and diabetic neuropathy (see Patent Document 2), Cushing's syndrome (see Patent Document 3), muscle wasting (see Patent Document 4), as well as diseases that will be more likely mediated by cellular immunity than by humoral immunity, such as tuberculosis, Hansen's disease, and psoriasis (see Patent Document 5).
As inhibitors of 11β-HSD1, various compounds have been reported previously, including thiazole derivatives, triazole derivatives, pyrrolidinone derivatives, and so on (see Patent Documents 6 to 19). In addition, there is a report of 2-adamantylurea derivatives (see Patent Document 20). However, there is no knowledge about derivatives relevant to the compounds of the present invention, i.e., tetrahydroquinoline derivatives, indoline derivatives, tetrahydrobenzoazepine derivatives, dihydrobenzoxazine derivatives, tetrahydroquinoxaline derivatives or dihydrobenzothiazine derivatives, each having a substituted adamantylaminocarbonyl group or a substituted adamantyloxycarbonyl group in their side chain. Moreover, these known 11β-HSD1 inhibitors cannot exert sufficient activity, and there is a demand for the development of compounds that have a therapeutic effect based on the inhibitory effect against 11β-HSD1 and that are satisfactory for use as pharmaceutical preparations.
Patent Document 1: International Publication No. WO06/055752
Patent Document 2: International Publication No. WO06/068992
Patent Document 3: International Publication No. WO06/066109
Patent Document 4: International Publication No. WO06/040329
Patent Document 5: International Publication No. WO05/110980
Patent Document 6: International Publication No. WO01/090090
Patent Document 7: International Publication No. WO01/090091
Patent Document 8: International Publication No. WO01/090092
Patent Document 9: International Publication No. WO01/090093
Patent Document 10: International Publication No. WO01/090094
Patent Document 11: International Publication No. WO03/065983
Patent Document 12: International Publication No. WO03/104207
Patent Document 13: International Publication No. WO05/108360
Patent Document 14: International Publication No. WO05/108368
Patent Document 15: International Publication No. WO06/024627
Patent Document 16: International Publication No. WO06/024628
Patent Document 17: International Publication No. WO06/048750
Patent Document 18: International Publication No. WO06/074244
Patent Document 19: International Publication No. WO06/104280
Patent Document 20: International Publication No. WO07/068,330